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linical Ca Rosas and Raez, J Clin Case Rep 2019, 9:12 C se f R o l e a p

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J Journal of Clinical Case Reports ISSN: 2165-7920

Case Report Open Access Anaphylactic Shock and Cardiac Arrest Secondary to Aprepitant Rosas D* and Raez LE Department of Thoracic Oncology Program, Memorial Cancer Institute/Memorial, Health Care System, Florida International University (FIU), Miami, Florida, USA

Abstract medications are commonly prescribed, especially in the Oncologic population. Every group of have their specific mechanism of action and side effect profile. There is little evidence that NK-1 can produce an anaphylactic shock. We report a case of a 57-year-old female diagnosed with advanced stage lung adenocarcinoma who received aprepitant as a premedication for chemotherapy that caused anaphylactic shock and cardiac arrest. The literature we found on due to aprepitant, were mainly case reports and case series. We encourage more research on this topic to come to the best treatment approach for these patients for a better outcome.

Keywords: Aprepitant; Neurokinin-1 receptor antagonist; Anti- Discussion emetic; Adverse drug reaction; Infusion reaction N/V are mediated by a feedback system between the gastrointestinal Introduction track and the Central Nervous System (CNS). That is why a combination of antiemetic regimes are directed against different targets on this The patient is of a 57-year-old female with past medical history of pathway. One of these pathways involves on the NK1 arthritis and former smoker for 30 years without any other medical receptors in the gastrointestinal tract and CNS, so targeting the NK1 history that was diagnosed with stage IV adenocarcinoma of the receptor with NK1 antagonist is one of the common treatments used lung with adrenal gland, left internal iliac and pararectal lymph node [9]. The most common antiemetic regimes used are a combination metastases. Next generation sequencing was negative for actionable of antagonist to 5-Hydroxytryptamine Type 3 (5HT3) receptor and mutations, PDL 1 status 50%, Micro Satellite Instability (MSI-H) to neurokinin 1 receptor, being these 2 medications combined with not detected She was started on chemoimmunotherapy regime with . Some regimes include a fourth medication, , IMPOWER 150: carboplatin+paclitaxel+bevacizumab+atezolizumab which is recommended by ASCO and NCCN guidelines [10-13]. and zolendronic acid for bone metastasis. Concomitantly, the patient Aprepitant and its , , are NK1 antagonists in was taking at home the following medications: , omeprazole, IV presentation. This presentation contains the nonionic surfactant , albuterol. During the first chemotherapy cycle the patient polysorbate 80 to solubilize the fosaprepitant. Polysorbate 80 is a had a minor rash after the infusion of aprepitant and the beginning of biologically active compound present in a few IV formulations, including paclitaxel that was managed with steroids and and docetaxel [14-16]. Hypersensitivity systemic reactions and infusion-site restarting the paclitaxel at slower rate. During the second cycle after adverse events during and after administration of these agents may be the administration of aprepitant and the first minutes of the paclitaxel partly due to the presence of polysorbate 80 in their preparation [17]. infusion the patient became hypotensive, developed a rash and had a Fosaprepitant is a medication used with dexamethasone and 5-HT3 alter mental status. The rapid response team was called and when she antagonist for N/V related to chemotherapy. It is of critical importance was being transported to the hospital, she developed cardiac arrest to encourage the monitoring of patients for hypersensitivity reactions and she needed to be resuscitated and intubated for the next 48 hours. that are not infusion site pain or thrombophlefitis and that they be Finally, she recovered well, was extubated and she was able to be treated followed in the initial and subsequent doses [17]. with pembrolizumab immunotherapy achieving disease stabilization , another NK1 antagonist, has the longest half-life for her lung cancer that lasted several months. of all NK1 antagonists but was removed from the market due to Case Report hypersensitivity reactions and anaphylaxis. Also, multiple NK1 RAs have potential drug–drug interactions. There have been two reports We present here the case of anaphylactic reaction after aprepitant with rolapitant causing severe infusion reactions [18]. We don’t infusion during the second cycle after having a minor anaphylactoid know the exact mechanism of anaphilaxis seen in the patient with reaction during the first cycle. Chemotherapy leads to nausea and fosaprepitant, raising the question: does the antagonism of NK receptor vomiting (N/V), and this significantly affects patient’s daily functioning, lead to anaphylaxis by other mechanisms other than increasing ability to eat and overall quality of life [1]. Patients with uncontrolled­ require more health care resources, show a greater health care costs, require a chemotherapy dose reduction or cycle delay that can ultimately *Corresponding author: Rosas D, Department of Thoracic Oncology Program, affect their outcome [2,3]. N/V incidence is multiple factor dependent Memorial Cancer Institute/Memorial, Health Care System, Florida International such as anxiety, female sex, and young age but the most important University (FIU), Miami, Florida, USA, Tel: +3364730701; E-mail: rosas.daniel@ icloud.com factor is the chemotherapy’s ability to cause emesis, also known as emetogenicity [4-7]. Guidelines stratify chemotherapy agents as having Received December 10, 2019; Accepted December 27, 2019; Published January a high moderate or low risk of inducing N/V. Without premedication, 04, 2020 high risk chemotherapy induces vomiting in 90% of patients who Citation: Rosas D, Raez LE (2019) Anaphylactic Shock and Cardiac Arrest receive it, and moderate risk in 30% to 90% of patients [8]. The time Secondary to Aprepitant. J Clin Case Rep 9: 1307 course of N/V has a relapsing characteristic, where patients experience Copyright: © 2019 Rosas D, et al. This is an open-access article distributed under N/V within 1 or 2 hours after starting the medications. Lasting around the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and 24 hours, later seising and reemerging at 48-72 hours [7]. source are credited.

J Clin Case Rep, an open access journal Volume 9 • Issue 12 • 10001307 ISSN: 2165-7920 Citation: Rosas D, Raez LE (2019) Anaphylactic Shock and Cardiac Arrest Secondary to Aprepitant. J Clin Case Rep 9: 1307

Page 2 of 2 substance P? The are some Nobel medications being studied for 4. Du-Bois A, Meerpohl HG, Kommoss FGM (1992) Course, patterns, and risk- factors for chemotherapy-induced emesis in -pretreated patients: A preventing and treating N/V due to chemotherapy. One of the novel study with ondansetron. Eur J Cancer 28: 450-457. agents is HTX-019. This agent has demonstrated a safety profile during a 30-minute infusion and a 2-minute injection in healthy volunteers. 5. Navari RM (2015) 5-HT3 receptors as important mediators of nausea and vomiting due to chemotherapy. Biochim Biophys Acta 10: 2738-2746. This study showed a tolerable safety profile in patients with cancer in a follow up prospective study and represents an alternative method 6. Roscoe JA, Morrow GR, Colagiuri B (2010) Insight in the prediction of chemotherapy-induced nausea. Support Care Cancer 18: 869-876. for N/V prevention. Cases of anaphylaxis after aprepitant infusion, have not been reported in the literature thus is important to show this 7. Hesketh PJ (2008) Chemotherapy-induced nausea and vomiting. N Engl J Med 358: 2482-2494. relationship between a commonly used medication ad a possible fatal outcome. Although anaphylaxis due to aprepitant is a rare entity, this 8. Steele RH, Limaye S, Cleland B (2005) Hypersensitivity reactions to the polysorbate contained in recombinant erythropoietin and darbepoietin. Nephrol type of pathology should be assessed by a multidisciplinary team for 10: 317-320. a better outcome. This case report shows the importance to have a 9. Ten-Tije AJ, Verweij J, Loos WJ (2003) Pharmacological effects of formulation broad differential diagnosis when it comes to anaphylactic reactions. vehicles: implications for cancer chemotherapy. Clin Pharmacokinet 42: Recognition of this kind of presentation is critical to institutions for 665-685. the appropriate diagnosis and evaluation for future pre chemotherapy 10. Herrstedt J, Roila F, Warr D (2017) 2016 Updated MASC/ESMO consensus protocols and medication adjustments. recommendations: Prevention of nausea and vomiting following high emetic risk chemotherapy. Support Care Cancer 25: 277-288. Conclusion 11. Coors EA, Seybold H, Merk HF (2005) Polysorbate 80 in medical products Anaphylaxis due to aprepitant is a very rare entity and we present and nonimmunologic anaphylactoid reactions. Ann Allergy Asthma Immunol 95: 593-599. the first case reported with aprepitant. We theorize that patients benefit from early recognition and treatment of this kind of adverse reaction, 12. Navari RM, Schwartzberg LS (2018) Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. OTT 11: 6459- but because of the low prevalence of this adverse effect, studies regarding 6478. a standardized treatment approach for this scenario are needed. Are there NK-1 antagonists an option, or is only supportive treatment an 13. Rojas C, Raje M, Tsukamoto T (2014) Molecular mechanisms of 5-HT3 and NK1 receptor antagonists in prevention of emesis. Eur J Pharmacol 722: 26-37. option? We hope that with reports like this raise awareness about the need to investigate and report the real prevalence of this uncommon 14. Hesketh PJ, Kris MG, Basch E (2017) Antiemetics: American society of clinical oncology clinical practice guideline update. J Clin Oncol 35: 3240-3261. complication. 15. Boccia R, Geller RB, Clendeninn N (2019) Hypersensitivity and infusion-site References adverse events with intravenous fosaprepitant after anthracycline-containing 1. Kreys ED, Kim TY, Delgado A (2014) Impact of cancer supportive care chemotherapy: A retrospective study. Future Oncol 15: 297-303. pathways compliance on emergency department visits and hospitalizations. J 16. Baxley A, Lee Z, Medina P (2018) Systemic hypersensitivity to fosaprepitant: A Oncol Pract 10: 168-173. report of two cases. J Oncol Pharm Pract 24: 76-78.

2. Craver C, Gayle J, Balu S (2011) Clinical and economic burden of 17. Cass AS, Odinet JS, Valgus JM (2019) Infusion reactions following chemotherapy-induced nausea and vomiting among patients with cancer in a administration of intravenous rolapitant at an academic medical center. J Oncol hospital outpatient setting in the United States. J Med Econ 14: 87-98. Pharm Pract 25: 1776-1783.

3. Kim HK, Hsieh R, Chan A (2015) Impact of CINV in earlier cycles on CINV 18. Navari RM, Mosier MC (2019) Crossover safety study of aprepitant: 2-min and chemotherapy regimen modification in subsequent cycles in Asia Pacific injection vs 30-min infusion in cancer patients receiving emetogenic clinical practice. Support Care Cancer 23: 293-300. chemotherapy. OTT 12: 3277-3284.

J Clin Case Rep, an open access journal Volume 9 • Issue 12 • 10001307 ISSN: 2165-7920